Recent Advances in Targeted Immunomodulatory Therapies for Chronic Ocular Surface Diseases

PURPOSE: To review and compare the mechanisms of action, clinical efficacy, and safety profiles of topical immunosuppressive and immunomodulatory agents for the management of chronic ocular surface diseases. METHODS: A comprehensive review of the literature was conducted using PubMed, Scopus, and Web of Science databases. Peer-reviewed clinical trials, observational studies, case series, and meta-analyses from 1960 to 2024 were included. Studies were selected based on their investigation of the efficacy and safety of topical therapies for chronic ocular surface diseases. Systemic therapies and non-ocular conditions were excluded. RESULTS: Corticosteroids remain effective in controlling acute inflammation but are associated with significant adverse effects, particularly with long-term use, including elevated intraocular pressure, cataract formation, and infection risk. In contrast, targeted immunomodulators such as cyclosporine, tacrolimus, lifitegrast, tofacitinib, and reproxalap provide more selective modulation of the immune response. These agents have demonstrated favorable tolerability and efficacy in chronic ocular surface diseases, including dry eye disease, vernal keratoconjunctivitis, and ocular GVHD. Recent advances include IL-1 receptor antagonists, JAK inhibitors, RASP inhibitors, and mitochondrial-targeted antioxidants. CONCLUSIONS: While corticosteroids are indispensable for acute management, targeted immunomodulatory therapies offer a safer and more sustainable approach for long-term treatment of chronic ocular surface inflammation. The emergence of novel topical agents supports a shift toward precision immunotherapy in ophthalmology.